Enkephalin action on the mesolimbic system: a dopamine-dependent and a dopamine-independent increase in locomotor activity.

Enkephalin has been identified by immunohistochemistry to be present in the vicinity of mesolimbic dopaminergic perikarya in the ventral tegmental area and axonal terminals in the nucleus accumbens. To evaluate the possibility that endogenous enkephalin may physiologically modulate the mesolimbic dopamine (DA) system, the effect of microinjection of the peptidase-resistant enkephalin analog, D-Ala2-Met5-enkephalinamide (DALA), in the ventral tegmental area and nucleus accumbens was examined. Locomotion and rearing behavior and alteration in concentration of DA and its metabolites in mesolimbic terminal areas were used to evaluate mesolimbic dopaminergic function. Microinjection of DALA into the ventral tegmental area produced a dose-dependent increase in locomotion and rearing which was antagonized by neuroleptic administration in the nucleus accumbens. Inasmuch as DALA administration into the ventral tegmentum was additive with a subthreshold dose of DA injected into the nucleus accumbens and produced a dose-related increase in 3,4-dihydroxyphenylacetic acid and the 3,4-dihydroxyphenylacetic acid/DA ratio, these data are consistent with the postulate that this treatment with DALA activates the mesolimbic DA system. DALA microinjection into the nucleus accumbens also produced a dose-dependent increase in locomotion and rearing. However, this behavioral effect was shown to be independent of the mesolimbic DA system because neither neuroleptic injection into the nucleus accumbens nor destruction of the mesolimbic DA system with 6-hydroxydopamine blocked the behavioral response produced by this treatment. Furthermore, DALA injection into the nucleus accumbens did not alter nucleus accumbens levels of DA or its metabolites at 15, 30 or 60 min after injection.(ABSTRACT TRUNCATED AT 250 WORDS)